scholarly journals Comparison of efficacy and safety of first-line palliative chemotherapy with EOX and mDCF regimens in patients with locally advanced inoperable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma: a randomized phase 3 trial

2015 ◽  
Vol 32 (10) ◽  
Author(s):  
Sebastian Ochenduszko ◽  
Miroslawa Puskulluoglu ◽  
Kamil Konopka ◽  
Kamil Fijorek ◽  
Katarzyna Urbanczyk ◽  
...  
Keyword(s):  
Palliative Chemotherapy ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Efficacy And Safety ◽  
First Line ◽  
Phase 3 ◽  
Gastroesophageal Junction Adenocarcinoma

MOUNTAINEER-02: Phase II/III study of tucatinib, trastuzumab, ramucirumab, and paclitaxel in previously treated HER2+ gastric or gastroesophageal junction adenocarcinoma—Trial in Progress.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS252-TPS252
Author(s):  
John H. Strickler ◽  
Yoshiaki Nakamura ◽  
Takayuki Yoshino ◽  
Daniel V.T. Catenacci ◽  
Yelena Y. Janjigian ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Open Label ◽  
Phase 3 ◽  
Double Blind ◽  
Gastroesophageal Junction Adenocarcinoma

TPS252 Background: Tucatinib (TUC), a highly selective HER2-directed TKI recently approved for HER2+ metastatic breast cancer (MBC), is being developed as a novel therapy for patients (pts) with metastatic colorectal cancer (mCRC) and other GI tumors. While trastuzumab (Tras) with chemotherapy is standard in the 1st-line setting for metastatic HER2+ gastric or gastroesophageal junction adenocarcinoma (GEC), no anti-HER2 therapy has demonstrated an OS benefit over chemotherapy in 2nd-line, possibly due to loss of HER2 expression following Tras-based therapy. In GEC xenograft models, dual targeting of HER2 with TUC and Tras showed superior activity to either agent alone. Interim results from the MOUNTAINEER study have shown promising activity for TUC and Tras in HER2+ mCRC. The MOUNTAINEER-02 study is evaluating the efficacy and safety of TUC in combination with Tras, ramucirumab (Ram), and paclitaxel (Pac) in pts with HER2+ GEC. Methods: MOUNTAINEER-02 (NCT04499924) is a phase 2/3 study evaluating TUC and Tras with the 2nd-line standard of care, Ram and Pac. Pts receive TUC 300 mg or placebo PO BID, Tras (6 then 4 mg/kg) or placebo (IV on Days 1 and 15 of each 28-day cycle), Pac (IV on Days 1, 8, 15), and Ram (IV on Days 1 and 15). Eligible pts have locally-advanced unresectable or metastatic HER2+ GEC, have received a HER2-directed antibody, and 1 prior line of therapy for advanced disease. Pts must be ≥18 years of age, with an ECOG ≤1, and have had no prior exposure to Ram, anti-HER2 or anti-EGFR TKI, HER2-directed antibody-drug conjugates, or taxanes ≤12 months before enrollment. Due to the potential impact of TUC on Pac metabolism, the study will include an initial Pac dose finding stage. The open-label phase 2 part will determine the recommended dose of Pac (60 or 80 mg/m²) combined with TUC, Tras, and Ram in 6-12 patients, and evaluate the safety and activity of the regimen in Cohorts 2A and 2B (30 patients each). The randomized, double-blind, phase 3 part will compare the efficacy and safety of TUC and Tras (Arm 3A; ~235 patients) vs. placebo (Arm 3B; ~235 patients), both in combination with Ram and Pac, and also evaluate activity of TUC with Ram and Pac (Arm 3C; ~30 patients). The dual primary phase 3 endpoints are OS and PFS per investigator, with confirmed ORR as a key secondary endpoint. HER2 status is determined at baseline using a blood-based NGS assay, and IHC/ISH of fresh or archival tumor biopsies, if available. Pts must be HER2+ by blood-based NGS in Cohort 2A and phase 3; in Cohort 2B, pts must be HER2+ in a biopsy taken post-progression during/after 1st-line therapy, but HER2-negative by blood-based NGS. Disease assessments per RECISTv1.1 will occur q6 weeks for 36 weeks, then q9 weeks. The pharmacokinetics of TUC, Pac, and their metabolites will be evaluated in a subset of pts, including a cohort with gastrectomies. Enrollment is ongoing in the U.S. Clinical trial information: NCT04499924.

Comparison of efficacy and tolerance of first-line palliative chemotherapy EOX and mDCF regimens in patients with locally advanced inoperable or metastatic gastric or gastroesophageal junction adenocarcinoma without overexpression of HER2 receptors.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 135-135 ◽  
Author(s):  
Sebastian Ochenduszko ◽  
Kamil Konopka ◽  
Miroslawa Puskulluoglu ◽  
Katarzyna Urbanczyk ◽  
Andrzej Budzynski ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Palliative Chemotherapy ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Grade 3

135 Background: The aim of the study was to compare efficacy and tolerance of first-line palliative chemotherapy EOX (epirubicin/oxaliplatin/capecitabine) and mDCF (docetaxel/cisplatin/5FU/leucovorin) regimens in patients with locally advanced inoperable or metastatic gastric or gastroesophageal junction adenocarcinoma without overexpression of HER2 receptors. Methods: Each chemotherapy regimen was assigned with 21 patients. Planned treatment consisted of 12 every-two-weeks mDCF cycles (docetaxel 40 mg/m2 day 1, leucovorin 400 mg/m2 day 1, 5FU 400 mg/m2 bolus day 1, 5FU 1000 mg/m2/d days 1 and 2, cisplatin 40 mg/m2 day 3) or 8 every-three-weeks EOX cycles (epirubicin 50mg/m2 day 1, oxaliplatin 130mg/m2 day 1, capecitabine 1250mg/m2/d days 1 to 21). The primary endpoint was overall survival in all patients who commenced at least one chemotherapy cycle. Results: Median progression-free survival was 5.8 months in EOX group and 7.5 months in mDCF group (p=0.11), and median overall survival was 8.5 months and 12.0 months respectively (p=0.219). Due to toxicity, patients in the EOX arm had more frequent reductions of cytostatics doses (42.9% vs 5.0%; p=0.009) as well as delays in the administration of subsequent chemotherapy cycles (81.0% vs 65.0%; p=0.424). Rates of all grade 3 or 4 adverse events were comparable between both arms (76.19% in the EOX vs 70.0% in the mDCF; p=1.000). Toxicities that occurred more frequently in the EOX group compared to mDCF group were: nausea (28.6% vs 5.0%; p=0.093), thromboembolic events (19.0% vs 10%; p=0.663) and grade 3 or 4 neutropenia (71.4% vs 55.0%; p=0.443). Conclusions: In this patients population with locally advanced inoperable or metastatic gastric or gastroesophageal junction adenocarcinoma without overexpression of HER2 receptors treatment with mDCF regimen was associated with a statistically non-significant 3.5 month longer median overall survival without increase in toxicity. Updated data will be presented.

Camrelizumab combined with SOX regimen in the first-line treatment of unresectable advanced or recurrent gastric cancer: A single-arm, prospective, open clinical study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16017-e16017
Author(s):  
Zhengxiang Han
Keyword(s):  
Gastric Cancer ◽  
Clinical Study ◽  
Advanced Gastric Cancer ◽  
Gastroesophageal Junction ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
First Line ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Recurrent Gastric Cancer ◽  
First Line Treatment

e16017 Camrelizumab combined with SOX regimen in the first-line treatment of unresectable advanced or recurrent gastric cancer£ºA single-arm, prospective, open clinical study. Background: Gastric cancer is one of the most common malignant tumors of the digestive system. In China, 80% of patients with gastric cancer are already in advanced or locally advanced stage at the time of detection. Even after receiving radical gastrectomy, more than half of patients will have local recurrence or distant metastasis, and the 5-year survival rate of patients with gastric cancer with metastasis is less than 10%.In recent years, more and more evidence supports the application of immune checkpoint inhibitors in advanced gastric cancer.In 2020, PD-1 was approved for advanced gastric cancer receiving second-line or above treatment in China, which is an affirming of the efficacy of PD-1 in the clinical treatment of gastric cancer. Immunotherapy combined with conventional chemotherapy, this study aims to explore the efficacy and safety of PD1 combined with chemotherapy in the treatment of first-line gastric cancer. Methods: This was a single center, prospective clinical study conducted at the Affiliated Hospital of Xuzhou Medical University, Jiangsu Province.Patients with newly treated unresectable advanced or recurrent gastric or gastroesophageal junction adenocarcinoma were enrolled.All enrolled subjects were treated with camrelizumab combined with SOX regimen every 3 weeks.The primary endpoint was progression-free survival (PFS).Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety.This study was registered at Chictr.org.cn with the number Chictr2000029691. Results: The study plans to enroll 30 patients, and 16 patients have been included in the study from March 2020 to December 2020. Among them, 7 patients can be evaluated, 14 males, 2 females, ECOG score 0 or 1. Of the 7 patients who can be evaluated for efficacy, 1 achieved PR and 5 achieved SD, ORR was 14.29%, and DCR was 85.71 %. This is the early stage of data analysis, PFS has not yet reached, and the side effects are mild, mainly with grade 1 adverse reactions. The most common AEs are neutropenia (3/7) and decreased appetite (2/7). There were no treatment-related deaths. Conclusions: This study provides preliminary evidence for the first-line treatment of unresectable advanced or recurrent gastric or gastroesophageal junction adenocarcinoma with camrelizumab combined with chemotherapy. The current number of enrolled cases is small, but the preliminary effect of immunotherapy combined with chemotherapy in first-line patients with advanced gastric cancer can still be seen. This trial will further explore the clinical efficacy and safety of immunotherapy in the first-line gastric cancer. Clinical trial information: ChiCTR2000029691.

KEYlargo: A phase II study of first-line pembrolizumab (P), capecitabine (C), and oxaliplatin (O) in HER2-negative gastroesophageal (GE) adenocarcinoma.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 228-228
Author(s):  
Hope Elizabeth Uronis ◽  
Christel Rushing ◽  
Gerard C. Blobe ◽  
Shiaowen David Hsu ◽  
Niharika B. Mettu ◽  
...  
Keyword(s):  
Phase Ii ◽  
Gastroesophageal Junction ◽  
Single Agent ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinical Activity ◽  
First Line ◽  
Tumor Biopsy ◽  
Gastroesophageal Junction Adenocarcinoma

228 Background: Gastric and esophageal adenocarcinomas are a leading cause of cancer death worldwide. Many of these patients (pts) present with locally advanced unresectable or metastatic disease and are treated with combination cytotoxic chemotherapy. Single agent P is FDA approved for patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (GEJ) whose tumors have a combined positive score (CPS) ≥ 1 after disease progression on or after two lines of therapy including fluoropyrimidine and platinum and her2/neu-targeted therapy (if indicated). More effective therapy is needed earlier in the disease trajectory. We conducted a single-arm phase II trial to establish the safety and efficacy of first-line C and O + P. Methods: Pts with previously untreated metastatic GE adenocarcinoma regardless of PDL-1 status received intravenous (IV) P 200mg with IV O 130mg/m2 every three weeks and oral C 850mg/m2 twice daily for 14 days on/7 days off. After the 6 patient safety cohort, pts first completed a biomarker cycle that included fresh tumor biopsy before P and one week after P before chemotherapy started. Archived FFPE tumor samples were also obtained from all pts with available tissue. The primary endpoint was progression free survival (PFS); secondary endpoints included response rate (RR) and overall survival (OS). Results: 36 pts were enrolled and 34 pts were evaluable for efficacy (1 pt withdrew for personal reasons before end of cycle 1 and 1 pt had immune-related toxicity during cycle 1 and was taken off study before any efficacy assessment). 9 pts (26%) had an esophageal primary, 18 pts (53%) had a GEJ primary and 7 pts (21%) had a gastric primary. Median PFS was 7.6 months [95% CI: 5.8 to 12.2], RR was 72.7% [95% CI: 57% to 88%], and median OS was 15.8 months [95% CI: 11.6 to NE]. 27 patients (81.8%) had decrease in disease burden (ranging from -19% to -100%). After > 18 months of follow-up, 5 patients remained in durable complete response (CR). Immune-mediated treatment related adverse events (TRAEs) included thyroid disorders (n=5; 14%), colitis (n=4; 11%), adrenal insufficiency (n=2; 5%), and type 1 diabetes (n=1). Sixteen patients (44%) experienced grade 3 or 4 TRAEs. There were no grade 5 TRAEs. Conclusions: The combination of C and O + P had acceptable safety and significant clinical activity. These promising results indicate that C and O + P merits further study as a first line option for patients with unresectable locally advanced or metastatic GE adenocarcinoma. Updated survival and correlative data will be presented. Clinical trial information: NCT03342937.

Camrelizumab combined with FLOFOX as neoadjuvant therapy for resectable locally advanced gastric and gastroesophageal junction adenocarcinoma: Updated results of efficacy and safety.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4036-4036
Author(s):  
Ying Liu ◽  
Guangsen Han ◽  
Hongle Li ◽  
Yuzhou Zhao ◽  
Zhi Li ◽  
...  
Keyword(s):  
Neoadjuvant Therapy ◽  
Clinical Stage ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
R0 Resection ◽  
Efficacy And Safety ◽  
D2 Lymph Node Dissection ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Therapy Strategy ◽  
Grade 3

4036 Background: Although anti-PD-1 antibody in combination with chemotherapy has shown promising antitumor activity in advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC), the evidence of neoadjuvant therapy for locally advanced GC/GEJC is limited. Camrelizumab combined FOLFOX as neoadjuvant therapy for resectable locally advanced GC/GEJC was a prospective, single-arm, phase 2 study we conducted. Here, we updated the results of efficacy and safety of this study. Methods: Patients confirmed by endoscopic ultrasonography (EUS) and imaging with clinical stage≥T2 and/or positive lymph nodes were enrolled. They received 4 cycles of camrelizumab (200mg ivgtt on day1, q2w) plus FOLFOX (oxaliplatin 85mg/m2 ivgtt, LV 200mg/m2 ivgtt, 5-Fu 400mg/m2 iv followed by 2.4mg/m2 CIV 46 hours on day 1, q2w) as neoadjuvant therapy. Then patients without disease progression evaluated by imaging underwent gastrectomy of D2 lymph node dissection. The primary endpoint was pCR, the secondary endpoints were R0 resection rate and safety. Results: Between Jul 24 2019 and Nov 30 2020, 49 patients were enrolled. The median age was 57 years (29-72 years). All patients completed 4 cycles treatment. Unfortunately, 2 of them were confirmed PD by imaging. In addition, two patients refused gastrectomy and withdrew from the study. Eventually, 45 patients underwent gastrectomy, of which 3 patients had intraperitoneal metastases during the operation. A total of 42 patients were evaluable, all of them gained R0 resection (100%), 4 patients (10%) achieved pCR and 10 patients (24%) reached TRG1. Among the patients experienced pCR, one of them was Her-2 positive, one was MSI-H, the rest two of them were PD-L1-positive (CPS≥10). The most common ≥grade 3 adverse events (AEs) were neutropenia (35%) and leukopenia (16%). Only 1 patient (2%) experienced grade 3 immune-related AEs of alanine aminotransferase and aspartate aminotransferase increase. No serious AEs resulted in termination of treatment or death. Conclusions: Camrelizumab combined with FOLFOX was an effective and safe neoadjuvant therapy strategy for patients with resectable locally advanced GC/GEJC. Furthermore, the analysis of biomarkers with clinical benefits is undergoing. Clinical trial information: NCT03939962. [Table: see text]

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